Ethanol → HCID 69316787, compound

HRID 1025530Notes

Reaction equation

HRID 1025530 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]=[C:13]([NH:23][CH2:24][C:25]4[CH:30]=[CH:29][C:28]([S:31]([NH2:34])(=[O:33])=[O:32])=[CH:27][CH:26]=4)[N:14]=[C:15](N4C=NN=C4)[C:16]=3[N:17]=2)=[CH:4][CH:3]=1.[CH3:35][CH2:36][O-:37].[Na+].CCO>C1COCC1.CN(C=O)C>[CH2:36]([O:37][C:15]1[C:16]2[N:17]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH:9]=[CH:10][C:11]=2[N:12]=[C:13]([NH:23][CH2:24][C:25]2[CH:26]=[CH:27][C:28]([S:31]([NH2:34])(=[O:33])=[O:32])=[CH:29][CH:30]=2)[N:14]=1)[CH3:35]

Participants

6

Reactant 3

HCID 702EthanolHCID 2723922Sodium ethoxideHCID 69103761HCID 69103761, compound

Product 1

HCID 69316787HCID 69316787, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 4-{[6-(4-fluoro-phenyl)-4-[1,2,4]triazol-4-yl-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}-benzenesulfonamide (638 mg, 1.34 mmol) in 10 ml THF was added to a solution of 21% (w/w) NaOEt in EtOH (1.50 ml, 4.03 mmol) in 20 ml of dry THF over 5 min. The triazole flask was rinsed once with 5 ml THF and the rinse was added to the reaction flask. The reaction was stirred at room temperature for 15 min. Analysis by reversed phase HPLC/MS indicated the reaction was complete. The pH was adjusted to 7 with 10% acetic acid/EtOAc and then concentrated in vacuo. The residue was partitioned between EtOAc and H2O. The aqueous layer was extracted twice with EtOAc. The combined organics were washed twice with water and once with brine, dried over MgSO4, filtered and concentrated. The solid was absorbed onto SiO2, and purified by eluting onto a 30 g SiO2 column with CH2Cl2/MeOH. The fractions containing the desired compound as determined by LC/MS were combined and concentrated. The solid thus obtained was dissolved in DMF and re-purified by reverse phase HPLC using acetonitrile/H2O in 4 runs. The pure fractions from each run were combined and the acetonitrile was removed in vacuo. The resulting aqueous suspension was neutralized with excess saturated aqueous NaHCO3, and extracted three times with EtOAc. The organics were dried over MgSO4, filtered and concentrated. The material was solidified by addition of MeOH. The solid was dried at high vacuum for 24 hrs, giving 110 mg of 4-{[4-ethoxy-6-(4-fluoro-phenyl)-pyrido[3,2-d]pyrimidin-2-ylamino]-methyl}-benzenesulfonamide (Example 109) as a white powder. MS (m/z) 454 [M+H]+.

Workup

  1. washThe triazole flask was rinsed once with 5 ml THF
  2. additionthe rinse was added to the reaction flask
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between EtOAc and H2O
  5. extractionThe aqueous layer was extracted twice with EtOAc
  6. washThe combined organics were washed twice with water and once with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe solid was absorbed onto SiO2
  11. custompurified
  12. washby eluting onto a 30 g SiO2 column with CH2Cl2/MeOH
  13. additionThe fractions containing the desired compound
  14. concentrationconcentrated
  15. customThe solid thus obtained
  16. customre-purified by reverse phase
  17. customthe acetonitrile was removed in vacuo
  18. extractionextracted three times with EtOAc
  19. dry with materialThe organics were dried over MgSO4
  20. filtrationfiltered
  21. concentrationconcentrated
  22. additionThe material was solidified by addition of MeOH
  23. customThe solid was dried at high vacuum for 24 hrs

Sources & evidence

ORD record
ord-2478d32fdcfe497b9aa5a4cb721b7b62
Source dataset
uspto-grants-2014_05
Patent number
US08729089B2

Reaction notes

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